UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

My research focuses on the evaluation of genetic events that contribute to the pathogenesis of thyroid cancer. The long-term goals of these studies are to translate these findings to improve diagnostic, treatment and prognostication strategies in patients with thyroid cancer.

The Role of Id Transcription Proteins in Thyroid Tumorigenesis

Over the past 3 years, we have begun to investigate the function of the Id proteins in thyroid tumors. We have focused on the expression and regulation of two particular Id proteins, Id1 and Id2, making use of our in-vitro thyroid cancer cell line model and thyroid cancer tissue bank. We have found that Id1 protein is an important regulator of cellular proliferation and differentiation in thyroid cancers. Our current efforts are centered on understanding the function of Id1 and Id2 proteins in thyroid cancer invasion, metastasis, and angiogenesis, and its potential as a therapeutic target gene in thyroid cancer.

Molecular Markers of Thyroid Neoplasms

Our cDNA array gene profiling studies have identified 7 candidate diagnostic and prognostic markers of malignant thyroid neoplasms. Based on these studies, we have developed a multigene assay to improve the diagnosis accuracy of thyroid nodule FNA biopsy and to better predict tumor behavior. We have begun to study the clinical utility and feasibility of applying these molecular markers to thyroid nodule FNA biopsy samples and as markers of disease aggressiveness.

Redifferentiation Therapy in Thyroid Cancers of Follicular Cell Origin

Because the expression of sodium-iodide symporter is critical for effective radioiodine uptake and therefore ablation of thyroid cancer cells, we are currently studying the effects of re-differentiating agents such as HDAC inhibitors in thyroid cancer cells. As a result of these studies, we have developed two clinical trials to evaluate re-differentiation therapy in patients who have differentiated thyroid cancers that are unresectable and unresponsive to radioiodine therapy.

Selected References

Kebebew E, Peng M, Wong MG, Ginzinger D, Duh QY, Clark OH. GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism. Surgery. Dec 2004;136(6):1261-1266.

Kebebew E, Peng M, Treseler PA, et al. Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid cancer cells. J Clin Endocrinol Metab. Dec 2004;89(12):6105-6111.

Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. Apr 1 2005;103(7):1330-1335.

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